In its progress from the basal layer (to which mitosis is normally restricted) toward the outer surface of the skin, the epidermal cell undergoes a programmed series of morphological changes which undoubtedly coincide with alterations in metabolic activities. Formation of the tonofilaments in the basal cell and the biogenesis of keratohyalin in the granular cell - combination of which appears to form the keratin fibers - must indicate the existence of specialized biochemical systems in these particular cells and must represent chemical steps in the differentiation of the epidermis. The etiologies of the basal carcinoma, the squamous cell carcinoma and psoriasis may involve aberrations in one or both of these biosynthetic processes. In addition, these pathologies appear to involve abnormalities in the control of mitosis. The overall objectives of this investigation at this time are (a) to develop a detailed molecular description of the metabolic pathways and the mechanisms of their control for the inhibition of mitosis in the differentiated cell, for the biogenesis of the tonofilaments in the basal and lower spinous cells and for the formation of keratohyalin in the granular cells and (b) to define the nature of the molecular lesions responsible for the pathology in psoriasis, squamous cell and basal cell carcinomas and possibly other diseases of aberrant differentiation by developing and applying technology suitable for investigating abnormalities in the parameters elucidated in (a), to biopsy specimens of the pathological lesions. BIBLIOGRAPHIC REFERENCES: Vaughan, F. L., Mitra, R. S. and Bernstein, I. A. (1976) Synthesis of DNA in Isolated Nuclei from Differentiated Mammalian Epidermal Cells, J. Invest. Dermatol. 66:355. Bernstein, I. A., Sachs, L., Ball, R. D. and Walker, G. (Dec., 1976) Regulation in Epidermal Differentiation in Biochemistry of Cutaneous Epidermal Differentiation, eds. Seiji, M. and Bernstein, I. A. University of Tokyo Press, Tokyo, Japan.